DESCRIPTION (Taken from the application): Recent clinical reports of apparent successful bisphosphonate therapy in children with osteogenesis imperfecta (OI) appear very promising. Previously, we demonstrated that the bisphosphonate, alendronate significantly, reduces fracture incidence and increase density in the growing oirn/oim mouse, an animal model of moderate-severe OI. However, data from that study also indicated that the quality of the newly formed bone was not optimal, and that reductions in long bone growth, might occur with treatment. However, since OI. is a heterogeneous disease clinically and most patients have unique mutations in collagen I formation, there may be a difference in response to treatment with bisphosphonates both short and long term. The long range goal of our studies is to evaluate bisphosphonate treatment in mouse models which have collagen abnormalities analogous to humans, i.e. ,decreased collagen content, abnormal collagen fibers, abnormal collagen packing. The proposed study will test the hypothesis that in 3 different mouse models of O.I. The first is the oim/oim mouse; the second a transgenic mouse which resembles mild-moderate O.I. The third is the new knock-in mouse (Brtl) which resembles mild O.I. The mice will be treated from age 2-14 weeks with alendronate. Bone quality will be assessed before and after treatment by radiographic analysis of the number of fractures, of bone and tooth density and geometry. Analysis of bone ultra structure and histology, and mechanical testing of whole bones; methodologies that have all been used successfully in our previous studies with oimj/oim mice. Investigation of specific aspects of alendronate treatment will provide information critical to the determination of how to proceed with individualized treatment of infants and children with different types of O.I.